Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. Methods: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. Results: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenoviruspositive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. Conclusion The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

This study performed the forensic anthropological sex estimation of Koreans in a non-metric way by reconstructing three-dimensional (3D) computed tomography (CT) images of skulls. The skull CT images used in this study were 100 (51 males, 49 females), and all CT images were taken with a slice thickness of 0.75 mm and then reconstructed into 3D images using the MIMICS 23.0 program. Using the reconstructed 3D image, measurements were repeated twice. The sex determination was male if the 4 point to 5 point was relatively more in five landmarks, and female if the points of 1 to 2 were relatively more. Results of the study show that, 88 of the 100 cases matched the actual sex. Among the 12 discrepant cases, ten cases were mismatched with the actual sex even though the estimation and repeated estimation readout of sexestimating were the same. Two cases, were “unknown,” showing different sexes in the first and repeated estimations. In conclusion, this study indicated that a forensic anthropological analysis from 3D images provided accurate point information on the landmarks of skulls, showing as high an accuracy as the sex estimation method using real bones. The ten cases of sex mismatch, except the two “Unknown” cases, are considered to be errors that did not consider differences in population groups. In further studies, further establishing a nonmetric, specifically Korean methods to increase the accuracy and reliability of sex estimation is need.

PURPOSE: Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal–regulated kinases (MEK)/extracellular signal–regulated kinases (ERK) pathways in the hippocampus. METHODS: Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. RESULTS: The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. CONCLUSIONS: Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.
Abdominal Wall ; Adenosine Monophosphate ; Blotting, Western ; Castration ; Cyclic AMP-Dependent Protein Kinases ; Down-Regulation ; Goserelin ; Hippocampus ; Immunohistochemistry ; Memory ; Memory, Short-Term ; Models, Animal ; Neurogenesis ; Orchiectomy ; Phosphorylation ; Phosphotransferases ; Spatial Memory

OBJECTIVE: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus casei in patients with CIN 3. METHODS: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. RESULTS: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. CONCLUSIONS: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02195089
Antibody Formation ; Biopsy ; Carcinoma in Situ ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Cohort Studies ; Female ; Humans ; Immunity, Humoral ; Immunization ; Lactobacillus casei ; Papillomavirus E7 Proteins ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms

PURPOSE: The aim of this study was to compare the long-term outcomes of total laparoscopic surgery with Natural Orifice Specimen Extraction (NOSE) with those for conventional laparoscopy (CL)-assisted surgery for treating rectal cancers. METHODS: We reviewed the prospectively collected records of 844 patients (163 NOSE and 681 CL) who underwent curative surgery for mid- or upper rectal cancers from January 2006 to November 2012. We applied propensity score analyses and compared oncological outcomes for the NOSE and CL groups in a 1:1 matched cohort. RESULTS: After propensity score matching, each group included 138 patients; the NOSE and CL groups did not differ significantly in terms of baseline clinical characteristics. The median follow-up was 57.7 months (interquartile range, 42.4–82.5 months). The combined 5-year local recurrence rate for all tumor stages was 4.1% (95% confidence interval [CI], 0.9%–7.4%) in the NOSE group and 3.0% (95% CI, 0%–6.3%) in the CL group (P = 0.355). The combined 5-year disease-free survival rates for all stages were 89.3% (95% CI, 84.3%–94.3%) in the NOSE group and 87.3% (95% CI, 81.8%–92.9%) in the CL group (P = 0.639). The postoperative mean fecal incontinence scores at 6, 12, and 24 months were similar between the 2 groups. CONCLUSION: In our experience, NOSE for mid- and upper rectal cancer had acceptable long-term oncologic outcomes comparable to those of conventional minimal invasive surgery and seems to be a safe alternative to reduce access trauma.
Case-Control Studies ; Cohort Studies ; Disease-Free Survival ; Fecal Incontinence ; Follow-Up Studies ; Humans ; Laparoscopy ; Natural Orifice Endoscopic Surgery ; Nose ; Propensity Score ; Prospective Studies ; Rectal Neoplasms ; Recurrence

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.
Adenocarcinoma* ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Female ; Follow-Up Studies ; Gynecology* ; Hematuria ; Humans ; Recurrence ; Retrospective Studies* ; Urinary Bladder Neoplasms ; Urinary Bladder*

S-methyl-(L)-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of −3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.
Animals ; Ethanol ; In Vitro Techniques* ; Mice ; Mice, Hairless ; Oleic Acid ; Skin Care ; Skin* ; Vitamin U ; Wound Healing

PURPOSE: To retrospectively compare minimally invasive percutaneous plate osteosynthesis (MIPPO) with open plate fixation for the treatment of clavicle midshaft fracture. MATERIALS AND METHODS: Between November 2011 to May 2014, 40 cases that were followed for more than 1 year–among all cases of MIPPO and open plate fixation–were analyzed. The study population was divided into two groups: group A included 20 cases of MIPPO and group B included 20 open plate fixation cases. The comparative analysis between the two groups was based on the operative time, bone union, functional evaluation (American Shoulder and Elbow Society score), incision length, pain relief (visual analogue scale, VAS), and complication. RESULTS: The bone union was successful for all the cases, and the functional evaluation scores of the shoulder joint were satisfactory for both groups (p>0.05). The operative time was 47.5 minutes and 58.7 minutes for group A and B, respectively (p<0.05). The incision length for group A was 6.2 cm and that for group B was 10.7 cm with statistical significance (p<0.05). Pain relief (VAS) after surgery for group A showed a quick recuperation in the early stages. For complications, there were 2 cases of dysesthesia and 1 case of malunion due to metal fixation failure in group A. There were 6 cases of dysesthesia and 2 cases of cosmetic problem due to hypertrophic scar in group B. CONCLUSION: Surgical results of clavicle shaft fracture were satisfactory for both groups, but group A had advantages of shorter operative time, minimal incision length, and better pain relief in the early stages compared with group B. However, we need further evaluations with long-term follow-up results and complications, such as malunion and exposure on radiation.
Cicatrix, Hypertrophic ; Clavicle* ; Elbow ; Follow-Up Studies ; Operative Time ; Paresthesia ; Retrospective Studies ; Shoulder ; Shoulder Joint